Originally known as Accomac Shire, was established in 1634 as one of the original eight shires of Virginia. The shire's name comes from the Native American word Accawmack, meaning "on the other side". In 1642 the name was changed to Northampton by the British, to eliminate "heathen" names in the New World. Northampton was split into two counties in 1663. The northern section assumed the original Accomac name, the southern, Northampton. In 1670, the Virginia Colony's Royal Governor William Berkeley abolished Accomac County, but the Virginia General Assembly re-created it in 1671. The very first Sheriff in the United States, William Stone, was appointed to serve Accomack County in 1634.

Unlike most of Virginia, during the Civil War, the county was not under Confederate control, but held by the forces of the United States government. In 1940, the General Assembly officially added a "k" to the end of the county's name to arrive at its current spelling. The name of "Accomack County" first appeared in the Decisions of the United States Board on Geographical Names in 1943.